Its subject is more precisely compositions based on a parasympatholytic agent, an adrenergic substance and advantageously a local anaesthetic, in the context of pre-operative treatment of the eye for a surgical operation on cataracts or laser treatment of the retina. These active ingredients are to be administered simultaneously on or in the eye.
According to a particularity of the invention, the parasympatholytic agent is a mydriatic agent and preferably a derivative of tropic acid such as a tropic acid ester or a tropic acid amide or a cyclohexyl or cyclopentylacetic acid amide.
Among these parasympatholytic agents, we shall notably mention cyclodrine, eucatropine, homatropine as well as atropine (benzylic ester of tropic acid), N-methyl hyoscine and especially tropicamide (N-ethyl 2-phenyl N-4 pyridyl methyl hydracrylamide or pyridyl methyl benzene acetamide).
Among the local anaesthetics, we shall more particularly mention butocaine, prilocaine, procaine, novocaine, tetracaine, ambucaine, amylocaine, bupivacaine, carticaine, butoxycaine, formocaine, mepivacaine, etidocaine, prilocaine, orthocaine, oxybuprocaine or benoxinate, and mainly lidocaine or diethylamino 2,6 dimethyl acetanilide, or one of its salts.
Among the adrenergic substances, we shall more particularly mention noradrenaline, phenylephrine, isoprenaline, dipivefrine, dimetrophine, norfenefrine, pholedrine or octedrine.
Combinations of this type have already been described in the literature.
Notably, the publication by Behndig A et al. (Acta Ophthalmologica Scandinavica (2004) 82(2) 144-147) describes the use of a composition containing 0.1% cyclopentolate, 1.5% phenylephrine and 1% lidocaine, designed for intracameral administration in the context of a surgical operation by phacoemulsification.
In this publication, the results obtained by intracameral injection of mydriatics were compared with those obtained by topical application. The effects, and especially the side effects, are no different. It appears to be important with this technique to avoid the general effects related to the administration of epinephrine or the intracameral administration of lidocaine.
Another publication (L. Apt et al. Am J. of Ophthalmology 89(4) (1980) 553-559) describes the use of ophthalmologic compositions containing tropicamide (0.5% or 1%) or cyclopentolate (0.5%) combined with phenylephrine at 2.5%, in instillation in the eye, one drop in each eye. In certain cases, instillation of the combination of two mydriatic agents is preceded by topical application of a drop of the anaesthetic proparacaine at 0.5%. The combination of three active ingredients is not envisaged, however.
Furthermore, S. A. Miller and W. F. Mieler have demonstrated (Canad. J. Ophtal 13 (1978) 291-293) the systemic effects resulting from subconjunctival injection of a combination of phenylephrine at a very high concentration (3.3%), cocaine (local anaesthetic at 1.3%) and atropine (0.3%), notably leading to an increase in blood pressure. This increase was followed by hypotension, pulmonary oedema and endocardial ischemia. The authors conclude by insisting on the dangerous effects on blood pressure of phenylephrine applied to the eye.
These triple combinations, notably the use of cyclopentolate as a parasympatholytic agent, at the concentrations indicated, are excluded from this invention.
These references, considered as the most similar in the prior art, show the need to effectively combine strong pharmacological action and nearly total absence of general effects resulting from the resorption in the eye of drugs having systemic effects.